类风湿性关节炎相关miRNA的鉴定以及血浆miRNA标志物的筛选与评价研究

项目名称： 类风湿性关节炎相关miRNA的鉴定以及血浆miRNA标志物的筛选与评价研究

项目编号： No.81473046

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 雷署丰

作者单位： 苏州大学

项目金额： 80万元

中文摘要： 类风湿性关节炎（RA）受复杂的遗传调控，但目前大多数遗传/表观遗传因子并未明。本项目将在40例RA和40例对照中，采用Illumina Solexa分别测序各例的外周血单个核细胞（PBMC）中的miRNA和mRNA，以及血浆miRNA，建立相应的表达谱，鉴定显著差异表达的miRNA，构建PBMC中miRNA与RA关联网络，以及miRNA与靶mRNA的调控网络。同时，筛选RA相关的血浆miRNA生物标志物，在另一独立样本（100RA vs.100对照）中验证标记物，并进行miRNA对T淋巴细胞的活化影响等深入的RA相关细胞分子功能研究。然后,在独立大样本（200RA vs. 200对照）中用ROC曲线等评价其RA诊断价值。本项目可能系统地筛选RA相关的miRNA表观遗传因素及评价血浆miRNA在RA诊断中的作用，为提高RA的临床诊断水平和开发RA早期干预和预防的方法和手段提供基础数据。

中文关键词： 分子流行病学；遗传流行病学；生物标志物；微小RNA

英文摘要： Rheumatoid arthritis (RA) has complex genetic determination, but most of specific genetic/epigentic factors are unknown. This study will sequence miRNA and mRNA from peripheral blood mononuclear cells (PBMCs) and miRNA from plasma for each subject using the Illumina Solexa in 40 RA cases and 40 controls, detect their corresponding expression profiles, identify significantly differential expressed miRNAs and set up PBMC association network of miRNA and RA as well as regulating network between miRNAs and their target mRNAs. This study will also screen RA-associated miRNA biomarkers from plasma. The detected biomarkers will be replicated the associations in another independent population (100RA vs.100 controls). Some molecular and cellular experiments (e.g., do the biomarkers have effects on the activation of T lymphocytes?) will be performed to detect the functional mechanism underlying the association between biomarkers and RA. The RA diagnostic value will be also evaluated for the identified miRNA biomarkers in another independent sample (200 RA vs. 200 controls), e.g., by ROC method. This study will systemically identify the RA associated miRNAs and evaluate their RA diagnostic values, which will improve the clinical diagnosis in RA and provide basic data for developing the methods and technologies of RA early diagnosis and intervention.

英文关键词： Molecular epidemiology;Genetic epidemiology;Biomarkers;Small RNA